Decoupling of structural and functional connectivity in hubs and cognitive impairment after mild traumatic brain injury.

Introduction Mild traumatic brain injury (mild TBI) exhibited abnormal brain network topologies associated with cognitive dysfunction. However, it was still unclear which aspects of network organization were critical underlying the key pathology of mild TBI. Here, a multi-imaging strategy was applied to capture dynamic topological features of both structural and functional connectivity networks (SCN and FCN), to provide more sensitive detection of altered FCN from its anatomical backbone and identify novel biomarkers of mild TBI outcomes. Methods 62 mild TBI patients (30 subjects as an original sample with 3-12 months follow-up, 32 subjects as independent replicated sample), and 37 healthy controls were recruited. Both diffusion tensor imaging (DTI) and resting-state fMRI were used to create global connectivity matrices in the same individuals. Global and regional network analyses were applied to identify group differences and correlations with clinical assessments. Results Most global network properties were conserved in both SCNs and FCNs in subacute mild TBI, whereas SCNs presented decreased global efficiency and characteristic path length at follow-up. Specifically, some hubs in healthy brain networks typically became non-hubs in patients and vice versa, such as the medial prefrontal cortex, superior temporal gyrus, middle frontal gyrus. The relationship between structural and functional connectivity (SC and FC) in patients also showed salient decoupling as a function of time, primarily located in the hubs. Conclusions These results suggested mild TBI influences the relationship between SCN and FCN, and the SC-FC coupling strength may be used as a potential biomarker to predict long-term outcomes after injury.